Diagnostic tools for soil-transmitted helminths control and elimination programs: A pathway for diagnostic product development

Lim, Mark D.; Brooker, Simon; Belizario, Vicente Y.; Gay-Andrieu, Françoise; Gilleard, John S.; Levecke, Bruno; Lieshout, Lisette van; Medley, Graham F.; Mekonnen, Zeleke; Mirams, Greg; Njenga, Sammy M.; Odiere, Maurice R.; Rudge, James W.; Stuyver, Lieven; Vercruysse, Jozef; Vlaminck, Johnny; Walson, Judd L.

doi:10.1371/journal.pntd.0006213

Cited by 54 publications

(71 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As numerous other countries move to consider a transition from STH control to elimination in focal geographic areas, documentation of what elimination actually can look like may be useful to policy makers seeking to implement changes in STH programmes. Furthermore, in addition to utility in settings with moderate to high prevalence [48,76,77], these data suggest that highly sensitive molecular techniques might also be useful for monitoring prevalence in areas where infection status is presumed to be quite low, as previously suggested [78], and can effectively rule out the presence of low-intensity infections that may pose a threat to sustained elimination. Continued economic development and application of governmental policies coupled with the expansion and improvement of MDA programmes for STH make the possibility of successfully moving from STH control to elimination an intriguing possibility.…”

Section: Discussionsupporting

confidence: 53%

What does soil-transmitted helminth elimination look like? Results from a targeted molecular detection survey in Japan

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background: Japan is one of the few countries believed to have eliminated soil-transmitted helminths (STHs). In 1949, the national prevalence of Ascaris lumbricoides was 62.9%, which decreased to 0.6% in 1973 due to improvements in infrastructure, socioeconomic status, and the implementation of national STH control measures. The Parasitosis Prevention Law ended in 1994 and population-level screening ceased in Japan; therefore, current transmission status of STH in Japan is not well characterized. Sporadic cases of STH infections continue to be reported, raising the possibility of a larger-scale recrudescence of STH infections. Given that traditional microscopic detection methods are not sensitive to low-intensity STH infections, we conducted targeted prevalence surveys using sensitive PCR-based assays to evaluate the current STH-transmission status and to describe epidemiological characteristics of areas of Japan believed to have achieved historical elimination of STHs.Methods: Stool samples were collected from 682 preschool-and school-aged children from six localities of Japan with previously high prevalence of STH. Caregivers of participants completed a questionnaire to ascertain access to water, sanitation and hygiene (WASH), and potential exposures to environmental contamination. For fecal testing, multi-parallel real-time PCR assays were used to detect infections of Ascaris lumbricoides, Necator americanus, Ancylostoma duodenale and Trichuris trichiura.Results: Among the 682 children, no positive samples were identified, and participants reported high standards of WASH. Conclusions:To our knowledge, this is the first STH-surveillance study in Japan to use sensitive molecular techniques for STH detection. The results suggest that recrudescence of STH infections has not occurred, and that declines in prevalence have been sustained in the sampled areas. These findings suggest that reductions in prevalence below the elimination thresholds, suggestive of transmission interruption, are possible. Additionally, this study provides circumstantial evidence that multi-parallel real-time PCR methods are applicable for evaluating elimination status in areas where STH prevalence is extremely low.

show abstract

Section: Discussionsupporting

confidence: 53%

What does soil-transmitted helminth elimination look like? Results from a targeted molecular detection survey in Japan

et al. 2020

Self Cite

View full text Add to dashboard Cite

show abstract

“…Currently, the microscopic detection and quantification of eggs excreted by adult worms in stool remains the standard diagnostic tool [9]. However, copromicroscopy lacks the performance to make well-founded decisions when a program reaches its endgame [10,11]. In fact, implementing these methods may potentially lead to substantial health and monetary consequences resulting from a premature stop decision.…”

Section: Introductionmentioning

confidence: 99%

“…As a response to this urgent need for improved diagnostic tools, the community summarized the desired characteristics-the so called target product profiles-for the different phases of the program (use-case #1: determine disease transmission and identify type of MDA, usecase #2: assess progress against program goals, use-case #3: confirm a decision to stop intervention and transition into surveillance and use-case #4: verify a sustained break in transmission; [10]). For the last two use-cases, the community concluded that the desired diagnostic biomarker should be in sufficient abundance in a readily accessible body fluid, excluding stool.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of copromicroscopy and serology to measure the exposure to Ascaris infections across age groups and to assess the impact of 3 years of biannual mass drug administration in Jimma Town, Ethiopia

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background The scientific community has recently summarized the desired characteristics for diagnostic tools across the different phases of a soil-transmitted helminth (STH) mass drug administration (MDA) program. Although serology meets some of the desired criteria, there is a scarcity of data on baseline serological profiles in human populations, both prior to and during MDA programs. Methods In this study, we compared the copromicroscopic and the serological infection profiles in 600 school-aged children (SAC) and 600 adults at the advent of the MDA program in Jimma Town, Ethiopia. The serological profiles were examined by two ELISAs that measure IgG4 responses to the Ascaris suum haemoglobin antigen (AsHb) and a somatic extract of lung stage larvae (AsLungL3). Three years into the MDA program, we sampled another group of 600 SAC from the same schools to assess the reduction in prevalence and intensity of Ascaris infections measured by copromicroscopy and serology.

show abstract

“…Some of the advantages of qPCR include the theoretical ability to detect single numbers of eggs present in the faeces due to its analytical sensitivity, to distinguish between species [22,23] and to achieve accurate results rapidly. Given these factors, qPCR may be the most likely currently available method to enable STH detection in pools in low-prevalence areas, especially when prevalence is close to the breakpoint of transmission [24]. For this reason, the use of PCR as part of a viable pooling strategy should be evaluated [25].…”

Section: Introductionmentioning

confidence: 99%

Pooling as a strategy for the timely diagnosis of soil-transmitted helminths in stool: value and reproducibility

et al. 2019

Self Cite

View full text Add to dashboard Cite

Background: The strategy of pooling stool specimens has been extensively used in the field of parasitology in order to facilitate the screening of large numbers of samples whilst minimizing the prohibitive cost of single sample analysis. The aim of this study was to develop a standardized reproducible pooling protocol for stool samples, validated between two different laboratories, without jeopardizing the sensitivity of the quantitative polymerase chain reaction (qPCR) assays employed for the detection of soil-transmitted helminths (STHs). Two distinct experimental phases were recruited. First, the sensitivity and specificity of the established protocol was assessed by real-time PCR for each one of the STHs. Secondly, agreement and reproducibility of the protocol between the two different laboratories were tested. The need for multiple stool sampling to avoid false negative results was also assessed. Finally, a cost exercise was conducted which included labour cost in low-and high-wage settings, consumable cost, prevalence of a single STH species, and a simple distribution pattern of the positive samples in pools to estimate time and money savings suggested by the strategy. Results: The sensitivity of the pooling method was variable among the STH species but consistent between the two laboratories. Estimates of specificity indicate a 'pooling approach' can yield a low frequency of 'missed' infections. There were no significant differences regarding the execution of the protocol and the subsequent STH detection between the two laboratories, which suggests in most cases the protocol is reproducible by adequately trained staff. Finally, given the high degree of agreement, there appears to be little or no need for multiple sampling of either individuals or pools. Conclusions: Our results suggest that the pooling protocol developed herein is a robust and efficient strategy for the detection of STHs in 'pools-of-five'. There is notable complexity of the pool preparation to ensure even distribution of helminth DNA throughout. Therefore, at a given setting, cost of labour among other logistical and epidemiological factors, is the more concerning and determining factor when choosing pooling strategies, rather than losing sensitivity and/or specificity of the molecular assay or the method.

show abstract

Diagnostic tools for soil-transmitted helminths control and elimination programs: A pathway for diagnostic product development

Cited by 54 publications

References 47 publications

What does soil-transmitted helminth elimination look like? Results from a targeted molecular detection survey in Japan

What does soil-transmitted helminth elimination look like? Results from a targeted molecular detection survey in Japan

Evaluation of copromicroscopy and serology to measure the exposure to Ascaris infections across age groups and to assess the impact of 3 years of biannual mass drug administration in Jimma Town, Ethiopia

Pooling as a strategy for the timely diagnosis of soil-transmitted helminths in stool: value and reproducibility

Contact Info

Product

Resources

About